Glycogen synthase kinase-3β is associated with the prognosis of hepatocellular carcinoma and may mediate the influence of type 2 diabetes mellitus on hepatocellular carcinoma.
Glycogen synthase kinase-3β is associated with the prognosis of hepatocellular carcinoma and may mediate the influence of type 2 diabetes mellitus on hepatocellular carcinoma.
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DOI：
10.1371/journal.pone.0105624
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shen F
中科院分区：
文献类型：
--
作者：
Qiao G;Le Y;Li J;Wang L;Shen F
尽管许多研究表明糖原合成酶激酶-3 β（glycogen synthase kinase-3 β，GSK-3β）与2型糖尿病（type 2 diabetes mellitus，T2 DM）及多种肿瘤有关，但GSK-3β在肝细胞癌（hepatocellular carcinoma，HCC）中的作用以及GSK-3β与T2 DM和HCC之间的相关性尚不清楚。本研究旨在探讨p-Ser 9-GSK-3β对肝癌患者预后的影响，并进一步了解T2 DM、GSK-3β与肝癌预后之间的相互作用。首先采用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法检测GSK-3β和p-Ser 9-GSK-3β在肝癌组织中的表达水平。然后，我们使用免疫组化染色来评估p-Ser 9-GSK-3β在178例肝癌根治性部分肝切除术后的表达模式。最后统计分析p-Ser 9-GSK-3β与T2 DM与HCC患者预后的关系。P-Ser 9-GSK-3β在肿瘤组织中的表达高于正常组织。相关和回归分析显示p-Ser 9-GSK-3β过表达与2型糖尿病的发生显著相关，相关系数为0.259（P = 0.001）。 多因素分析显示，p-Ser 9-GSK-3β的过度表达（P<0.001）和T2 DM（P = 0.008）分别是HCC预后不良的独立相关因素。 进一步的分析表明，这两个变量是密切相关的。p-Ser 9-GSK-3β过表达和T2 DM与HCC手术预后差密切相关。P-Ser 9-GSK-3β可能在T2 DM影响HCC预后中起重要作用。
Although many studies have shown glycogen synthase kinase-3β(GSK-3β) was associated with type 2 diabetes mellitus(T2DM) and implicated with a wide range of cancers, the role of GSK-3β in hepatocellular carcinoma(HCC) and the correlation among GSK-3β, T2DM and HCC remains unclear. Our objectives were to identify the effect of p-Ser9-GSK-3β on the prognosis of patients with HCC and to learn more about the interaction among T2DM, GSK-3β and the prognosis of HCC. Firstly we used reverse transcriptase-PCR(RT-PCR) and western blotting to determine the expression levels of GSK-3β and p-Ser9-GSK-3β in human HCC samples. We then used immunohistochemical staining to evaluate the expression pattern of p-Ser9-GSK-3β in 178 patients with HCC after curative partial hepatectomy. Finally we statistically analyzed the association of p-Ser9-GSK-3β and T2DM with the prognosis of patients with HCC. P-Ser9-GSK-3β was over-expressed in tumor tissues compared with their normal counterparts. Correlation and regression analysis indicated that the over-expression of p-Ser9-GSK-3β was significantly associated with T2DM, and the correlation coefficient was 0.259 (P = 0.001). Multivariate analysis showed that the over-expression of p-Ser9-GSK-3β(P<0.001) and T2DM(P = 0.008) were independently associated with poor prognosis of HCC, respectively. Further analysis demonstrated that these two variables are closely related with each other. The over-expression of p-Ser9-GSK-3β and T2DM are strongly correlated with worse surgical outcome of HCC. P-Ser9-GSK-3β may play a significant role in mediating the influence of T2DM on the prognosis of HCC.
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